We recently developed a mouse model of appetitive operant aggression and reported that adult male outbred CD-1 mice lever-press for the opportunity to attack subordinate male mice and relapse to aggression seeking during abstinence. Here we studied the role of nucleus accumbens (NAc) dopamine receptor (Drd)1- and Drd2-expressing neurons in aggression self-administration and aggression seeking. We trained CD-1 mice to self-administer intruders (9 d, 12 trials/d) and tested them for aggression self-administration and aggression seeking on abstinence Day 1. We used immunohistochemistry and in situ hybridization to measure the neuronal activity marker Fos in the NAc, and cell-type-specific colocalization of Fos with Drd1- and Drd2-expressing neurons. To test the causal role of Drd1- and Drd2-expressing neurons, we validated a transgenic hybrid breeding strategy crossing inbred Drd1-Cre and Drd2-Cre transgenic mice with outbred CD-1 mice and used cell-type-specific Cre-DREADD (hM4Di) to inhibit NAc Drd1- and Drd2-expressing neuron activity. We found that aggression self-administration and aggression seeking induced higher Fos expression in NAc shell than in core, that Fos colocalized with Drd1 and Drd2 in both subregions, and that chemogenetic inhibition of Drd1-, but not Drd2-, expressing neurons decreased aggression self-administration and aggression seeking. Results indicate a cell-type-specific role of Drd1-expressing neurons that is critical for both aggression self-administration and aggression seeking. Our study also validates a simple breeding strategy between outbred CD-1 mice and inbred C57-based Cre lines that can be used to study cell-type and circuit mechanisms of aggression reward and relapse.SIGNIFICANCE STATEMENT Aggression is often comorbid with neuropsychiatric diseases, including drug addiction. One form, appetitive aggression, exhibits symptomatology that mimics that of drug addiction and is hypothesized to be due to dysregulation of addiction-related reward circuits. However, our mechanistic understanding of the circuitry modulating appetitive operant aggression is limited. Here we used a novel mouse model of aggression self-administration and relapse, in combination with immunohistochemistry, in situ hybridization, and chemogenetic manipulations to examine how cell types in the nucleus accumbens are recruited for, and control, operant aggression self-administration and aggression seeking on abstinence Day 1. We found that one population, dopamine receptor 1-expressing neurons, act as a critical modulator of operant aggression reward and aggression seeking.
Pubmed ID: 30655356 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This monoclonal targets mCherry
View all literature mentionsThis monoclonal targets Phospho-c-Fos (Ser32) (D82C12) XP Rabbit mAb
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis polyclonal targets IgG (H+L)
View all literature mentionsSoftware package used for interactive, or batched, statistical analysis in social science, health sciences and marketing. Software platform offers advanced statistical analysis, a library of machine-learning algorithms, text analysis, open-source extensibility, integration with big data and deployment into applications.Versions that were produced by SPSS Inc. before the IBM acquisition (Versions 18 and earlier) would be given origin or publisher of SPSS Inc. in Chicago.
View all literature mentionsSoftware package for control of automated microscopes. Cross-platform desktop application, to control motorized microscopes, scientific cameras, stages, illuminators, and other microscope accessories.
View all literature mentionsMicroscopy imaging software for image acquisition, processing, measurement, and analysis. iVision‐Mac directly supports the acquisition of images and time-lapse series.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsMus musculus with name Crl:CD1(ICR) from IMSR.
View all literature mentionsThis monoclonal targets Phospho-c-Fos (Ser32) (D82C12) XP Rabbit mAb
View all literature mentionsThis monoclonal targets Phospho-c-Fos (Ser32) (D82C12) XP Rabbit mAb
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis polyclonal targets IgG (H+L)
View all literature mentionsThis monoclonal targets mCherry
View all literature mentionsSoftware package used for interactive, or batched, statistical analysis in social science, health sciences and marketing. Software platform offers advanced statistical analysis, a library of machine-learning algorithms, text analysis, open-source extensibility, integration with big data and deployment into applications.Versions that were produced by SPSS Inc. before the IBM acquisition (Versions 18 and earlier) would be given origin or publisher of SPSS Inc. in Chicago.
View all literature mentionsSoftware package for control of automated microscopes. Cross-platform desktop application, to control motorized microscopes, scientific cameras, stages, illuminators, and other microscope accessories.
View all literature mentionsMicroscopy imaging software for image acquisition, processing, measurement, and analysis. iVision‐Mac directly supports the acquisition of images and time-lapse series.
View all literature mentions